Factors Influencing the Occurrence of “on‐off” Symptoms during Long‐Term Treatment with L‐dopa

Abstract

On-off symptoms developed in 43 of 85 parkinsonian patients who were treated with L-dopa for 5 yr or more, the risk of such symptoms apparently being greater the younger the patient was at the onset of the disease and at the start of treatment. The dopa dose had been higher throughout the treatment in the patients developing on-off symptoms than in those maintaining an even effect, and the initial improvement had been more marked and dyskinesia had appeared earlier and in a higher frequency. The clinical observations seemed to be related to some pharmacological findings, where different degrees of the nigrostriatal neuron degeneration and the efficacy of the remaining neurons could be of importance for a varying therapeutic response. It also seemed possible that a higher dopa could evoke on-off symptoms more easily than a lower one in predisposed individuals. As the patients maintaining an even symptomatology during long-term treatment with L-dopa were older, and in particular as they had dementia in a higher frequency than those developing on-off symptoms, the possibility of a more widespread neuron damage, influencing the clinical manifestation in these patients, had to be taken into consideration.